Targeting tiny genetic switches in gene messages to treat inherited diseases
Identifying regulatory uORFs as a targetable axis for hereditary disease
This project tests whether small sequences at the front of gene messages can be changed to raise or lower protein levels for people with inherited disorders.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pennsylvania NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11113825 on NIH RePORTER |
What this research studies
Researchers will search large human genetic databases (like gnomAD, the Penn Medicine BioBank, and the UK Biobank) to find short regulatory sequences called upstream open reading frames (uORFs) that affect how much protein a gene makes. They will build a searchable, public database of these uORFs and use computer models to rank the most promising targets. Laboratory experiments using cell-based luciferase assays will check whether altering those uORFs actually changes protein output. The team will iterate between the computer predictions and lab results to refine which uORFs are best suited for future therapies.
Who could benefit from this research
Good fit: People with inherited conditions caused by abnormal protein levels—such as disorders linked to specific genes like BMPR2—would be the most relevant group for this research.
Not a fit: Patients with non-genetic problems (for example infections, injuries, or conditions not driven by gene expression changes) are unlikely to benefit directly from this work.
Why it matters
Potential benefit: If successful, this work could uncover new drug targets that let doctors increase or decrease specific proteins to treat some hereditary diseases.
How similar studies have performed: Laboratory studies have shown uORFs can control protein production, but using them broadly as therapeutic targets is a relatively new and largely unproven strategy in patients.
Where this research is happening
Philadelphia, United States
- University of Pennsylvania — Philadelphia, United States (Active)
Researchers
- Principal investigator: Barash, Yoseph — University of Pennsylvania
- Study coordinator: Barash, Yoseph
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.